Description: (Applicant's Description) The Cell Cycle Disregulation Program comprises members from a wide variety of disciplines. The program is designed to integrate multidisciplinary studies on cell cycle control with questions concerning preneoplastic initiation, progression, and treatment. The program approaches these questions through a variety of methods which include cell biology, genetics, molecular biology, and biochemistry. Organization of the program is arranged into three major areas: 1) regulated entry into the cell division cycle; 2) the characterization of the molecular components of the cell cycle engine and its control; and 3) the fidelity and disregulation of cell cycle control. The examination of these processes in normal and neoplastic tissues should provide information about key steps in neoplastic transformation and aid in the identification of molecular targets for effective therapy. Comparison of critical processes between tissues and between species may also provide important insights given documented differences in carcinogenic frequency. Many members also belong to organ/site-specific programs within the Cancer Center, which will facilitate a mutual exchange of information with clinical personnel. Interactions will be stimulated through a weekly research seminar series, an annual retreat, and informal discussion groups examining the basis of carcinogenesis.